Serum Steroid Profiling in the Diagnosis of Adrenocortical Carcinoma: A Prospective Cohort Study

Context Guidelines suggest performing urine steroid profiling in patients with indeterminate adrenal tumors to make a noninvasive diagnosis of adrenocortical carcinoma (ACC). However, urine steroid profiling is not widely available. Objective To determine the accuracy of clinically available serum 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone in diagnosing ACC. Methods We conducted a prospective single-center cohort study of patients with adrenal masses evaluated between 2015 and 2023. Serum was analyzed by liquid chromatography-mass spectrometry for 17OH-pregnenolone, 17OH-progesterone, and 11-deoxycortisol. Reference standard for adrenal mass included histopathology, imaging characteristics, imaging follow up of 2 years, or clinical follow up of 5 years. Localized Generalized Matrix Learning Vector Quantization analysis was used to develop serum steroid score and assessed with area under receiver operating curve. Results Of 263 patients with adrenal masses, 44 (16.7%) were diagnosed with ACC, 161 (61%) with adrenocortical adenomas (ACAs), 27 (10%) with other adrenal malignancies, and 31 (12%) with other. Hounsfield unit >= 20 was demonstrated in all ACCs, in all but 1 other adrenal malignancy, and in 58 (31%) ACAs. All 3 steroids were higher in patients with ACCs vs non-ACCs, including when comparing ACCs with functioning ACAs, and with ACAs with Hounsfield unit >= 20 (P < .0001 for all). Localized Generalized Matrix Learning Vector Quantization analysis yielded a serum steroid score that discriminated between ACC and non-ACC groups with a mean threshold fixed area under receiver operating curve of 0.823. Conclusion We showed that measurements of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone could be valuable in diagnosing ACC. After appropriate validation, serum steroid score could be integrated in clinical practice.